In an effort to identify new antimicrobial compounds with a mechanism of action different to those of conventional antibiotics, both pharmaceutical and biotechnology companies have turned their attention to antimicrobial peptides.
Naturally-occurring antimicrobial peptides are evolutionary conserved components of the host's innate immunity system that form the first line of defense against infections. They have been identified in almost all classes of life. In this respect, antimicrobial peptides are generally defined as peptides with direct antibiotic activity, having fewer than about 50 amino acids and having a net positive charge. To date, more than 600 peptides (in virtually all species of life) have been described which not only kill pathogenic microorganisms, including Gram-positive and Gram-negative bacteria, viruses, protozoa and fungi, but also play a role in recruiting and promoting elements of the innate immune system.
The significant advantage of antimicrobial peptides resides in their mechanism of action, which is markedly different from that of conventional antibiotics. Although the precise mechanism of the broad spectrum of antimicrobial activity of these peptides is not yet fully understood, they appear to act via a specific, but not receptor-mediated, formation of transmembrane pores or ion channels on cellular membrane. This causes leakage of essential metabolites that results in the disruption of microbial cell structure and leads to cell death. In contrast to conventional antibiotics, they do not appear to induce microbial resistance and require only short time to induce killing. As the growing resistance of bacterial pathogens to conventional antibiotics has become serious global health problem, this alarming situation resulted in a search for novel alternative to traditional antibiotics such as antimicrobial peptides.
Given the complexity of microorganisms of potential or real pathogenicity to animals and humans, there is a clear need for a diverse range of effective antimicrobials e.g., having a broad spectrum or a spectrum of activity that complements existing therapeutics e.g., known antibiotics or antimicrobial proteins. There also remains a need for antimicrobial proteins having specific activity comparable to that of existing antibiotic treatments, preferably without the development of the resistance that occurs to conventional antibiotic compounds. There is also a need for antimicrobials that are effective in a wide range of applications, including the food, agriculture and horticulture industries, and in medicine, veterinary science and phytopathology. Clearly, it is highly desirable for any antimicrobial composition of matter to exhibit reduced toxicity and high activity at physiological conditions, e.g., at physiological salt concentrations. In addition, it would also be an advantage to have antimicrobial peptides with a low number of aminoacids as this would simplify its synthesis and purification.